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Immune cell composition in unipolar depression: a comprehensive systematic review and meta-analysis.Molecular Psychiatry Jan 2023Depression has been associated with inflammatory pathophysiological mechanisms, including alterations in amount of circulating immune cells. However, no meta-analysis... (Meta-Analysis)
Meta-Analysis
Depression has been associated with inflammatory pathophysiological mechanisms, including alterations in amount of circulating immune cells. However, no meta-analysis within the past 20 years have reevaluated the circulating immune cells in blood and cerebrospinal fluid (CSF) from patients with depression compared to healthy controls. The aim of this study was to systematically evaluate the circulating immune cells in blood and CSF from patients with unipolar depression compared to healthy controls. Databases were searched up until February 12, 2021. Data-extraction was performed by two independent reviewers. 104 studies were included in the meta-analysis using fixed and random-effects models. Patients with depression had a significantly higher overall leukocyte count (35 studies; SMD, 0.46; 95% CI: 0.31-0.60, I = 68%), higher neutrophil count (24 studies; SMD, 0.52; 95% CI: 0.33-0.71, I = 77%) and higher monocyte count (27 studies; SMD, 0.32; 95% CI: 0.11-0.53, I = 77%) compared to healthy controls. Leukocyte counts were higher in inpatients, indicating a relation to depression severity. Furthermore, there were significant alterations in several lymphocyte subsets, including higher natural killer cells and T cell subsets. Higher neutrophil/lymphocyte ratio (11 studies; SMD = 0.24; 95% CI: 0.06-0.42, I = 73%), CD4/CD8 cell-ratio (26 studies; SMD = 0.14; 95% CI: 0.01-0.28, I = 42%) and T helper 17/T regulatory ratio (2 studies; SMD = 1.05; 95% CI: 0.15-1.95, I = 86%) were found in patients compared to healthy controls. CSF white cell count was higher in patients compared to controls (3 studies; SMD = 0.20; 95% CI: 0.01-0.38, I = 0%). There were no data for CSF cell subsets. This study suggests that there are several blood immune cell alterations in patients with unipolar depression compared to healthy controls, both in major leukocyte subsets and more specialized immune cell subsets.
Topics: Humans; Depressive Disorder; Neutrophils
PubMed: 36517638
DOI: 10.1038/s41380-022-01905-z -
Journal of Medical Economics 2022To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma. (Meta-Analysis)
Meta-Analysis
AIMS
To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma.
MATERIALS AND METHODS
Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.
RESULTS
Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.
LIMITATIONS
Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses.
CONCLUSIONS
Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Eosinophils; Humans; Omalizumab
PubMed: 35570578
DOI: 10.1080/13696998.2022.2074195 -
Journal of Oral Pathology & Medicine :... May 2018Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2... (Meta-Analysis)
Meta-Analysis Review
Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Databases, Bibliographic; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Macrophages; Male; Middle Aged; Prognosis; Receptors, Cell Surface; Tumor Microenvironment; Young Adult
PubMed: 28940738
DOI: 10.1111/jop.12643 -
PloS One 2019Many studies have investigated the association between the level of myeloid derived suppressor cells (MDSCs) and clinical features and prognosis of hepatocellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Many studies have investigated the association between the level of myeloid derived suppressor cells (MDSCs) and clinical features and prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. This systematic review and meta-analysis was conducted to summarize all available data and estimate the relationship.
METHODS
A comprehensive literature review was carried out using Medline, Embase and Web of Science database through December 2018 to identify relevant studies. The standardized mean difference (SMD) and the hazard ratio (HR) with 95% confidence interval (CI) were utilized for evaluating continuous outcomes and survival analysis, respectively. All statistical analyses were performed by STATA 14.0 software.
RESULTS
A total of 13 studies with 1002 HCC patients were included in the meta-analysis. Overall, the proportion of MDSCs in HCC patients was higher than that in healthy controls (SMD = 4.49, 95% CI = 2.53-6.46, P<0.001), and patients with chronic liver disease (SMD = 3.41, 95% CI = 1.58-5.24, P<0.001). Subgroup analysis based on the phenotypes of MDSCs and geographical areas showed similar results. However, the frequency of MDSCs was not affected by the treatment with conventional approaches for HCC (SMD = -0.25, 95% CI = -0.57-0.06, P = 0.119). Moreover, increased MDSCs level was significantly associated with poorer overall survival (HR = 2.36, 95% CI = 1.70-3.29, P<0.001) and recurrence-free survival (HR = 2.72, 95% CI = 1.70-4.35, P<0.001), but not significantly correlated with any clinicopathological parameters.
CONCLUSION
The results of this systematic review suggest that elevated MDSCs level appears to be associated with an increased risk for disease progression and poor prognosis for HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease Progression; Disease-Free Survival; Humans; Liver Neoplasms; Myeloid-Derived Suppressor Cells; Neoplasm Recurrence, Local; Phenotype; Prognosis; Risk
PubMed: 31790437
DOI: 10.1371/journal.pone.0225327 -
Autoimmunity Reviews Feb 2021Nuclear Factor Kappa-Β (NF-kB) is recognized as one of the main inflammatory pathways in the Autoimmune Disease (AD) Rheumatoid Arthritis (RA), which exhibits high...
Nuclear Factor Kappa-Β (NF-kB) is recognized as one of the main inflammatory pathways in the Autoimmune Disease (AD) Rheumatoid Arthritis (RA), which exhibits high levels of inflammatory cytokines such as IL-1, TNFa and IL-6 linked to bone erosion and disease progression. NF-kB is also the most studied pathophysiological mechanism in RA, however, over the last few decades, a more recently discovered Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL), also linked to NF-kB activation and bone erosion, has been the topic of interest for research in the area of AD management. As the non-discriminative long term suppression of the NF-kB pathway by pharmacological agents in the management of RA has been linked with a number of side effects and with the discovery of the RANKL mechanism, which may present a more targeted approach to the management of the AD, there has been renewed interest in research on the potential impact of nutritional interventions influencing the NF-kB pathway, RANKL as well as RA disease outcomes. Existing research highlights the potential utility of nutrients such as Omega 3 and Vitamin D, which may lower NF-kB activation in RA. There is, however, a gap in the knowledge of the effects of nutritional interventions on pathophysiological mechanisms contributing to RA and a more robust systematic analysis of whether nutrients or specific vitamins can have an effect on the NF-kB and RANKL main drivers of pathology in RA. Findings from this study suggest the potential of Vitamin D supplementation in lowering the levels of RANKL and related markers/cytokines such as Th17 cell levels, OPG/RANKL ratio and CXCL10 pathway, which may present as a viable nutrition intervention for the management of RA. The methodology of this review involved a Systematic Search of the Literature with a Critical Appraisal of papers. It incorporated three tranche searches of 1. review, 2. animal/in vitro and 3. intervention peer reviewed research published in the last 10 years, resulting in a total of 119 papers. Results provide an overview of the NF-kB pathway, a detailed mechanistic examination of the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL) which is linked to bone erosion, and finally a review of nutritional interventions relating to this mechanism of pathophysiology. The accepted papers were critically appraised using SIGN50 for human studies and the ARRIVE guidelines for animal studies; the narrative was and the extracted information coded into key themes.
Topics: Animals; Arthritis, Rheumatoid; Humans; Ligands; NF-kappa B; Osteoclasts; Osteoprotegerin; RANK Ligand
PubMed: 33340772
DOI: 10.1016/j.autrev.2020.102741 -
Oral Oncology Dec 2022Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment... (Meta-Analysis)
Meta-Analysis Review
Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment (TME). In this systematic review and meta-analysis, studies assessing tumor infiltration with CD68+, iNOS+, HLA-DR+, CD11b+, CD163+, CD206+, and CD204+TAMs were included, and correlation to survival hazard was studied. A low number of CD68+TAMs correlated to better overall survival (OS) in multivariate analysis (HR 1.36 95 %CI (1.07-1.72) P = .01). CD68+TAMs did not correlate to disease free survival (DFS), disease specific survival (DSS), progression free survival (PFS), or recurrence free survival (RFS). A low number of CD163+TAMs correlated to better OS in uni- and multivariate analysis (resp. HR 2.65 95 %CI (1.57-4.46) P = .01 and HR 2.42 95 %CI (1.72-3.41) P < .001). A low number of CD163+TAMs also correlated to better DFS and PFS, whereas a low number of CD204+TAMs only correlated to PFS. While IHC analysis of pan macrophage marker CD68 and M2-like marker CD163 both show prognostic utility in OS, CD163 is a stronger prognosticator, as indicated by multivariate meta-analysis. CD163+TAMs also correlate to DFS and PFS; outcomes that are more relevant to patients, thus showing promising results for future clinical implementation.
Topics: Humans; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tumor-Associated Macrophages; Antigens, Differentiation, Myelomonocytic; Tumor Microenvironment; Head and Neck Neoplasms
PubMed: 36335818
DOI: 10.1016/j.oraloncology.2022.106227 -
Prostate Cancer and Prostatic Diseases Mar 2023Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its efficacy. Some preclinical studies explored the role of MDSCs in prostate cancer development. We aimed to verify the availability of studies exploring the prognostic effect of circulating MDSCs in prostate cancer patients.
METHODS
We systematically selected studies for a meta-analysis, which compares survival between prostate cancer patients with high vs low circulating MDSC levels. We extracted or calculated hazard ratios (HRs) and relative 95% confidence intervals (CIs) in terms of overall survival (OS) from selected studies. We calculated the pooled HR and relative 95% CIs and estimated publication bias.
RESULTS
Among 133 studies retrieved from search on Pubmed, 5 eligible studies (236 prostate cancer patients) met inclusion criteria. High circulating MDSC levels are associated with a worse OS (HR = 2.19; 95%CI = 1.51-3.17). Heterogeneity was not significant (I = 0%; p = 0.64). Publication bias was also not significant (Egger's test, p = 0.09).
CONCLUSIONS
High levels of circulating MDSCs induce a worse OS in prostate cancer patients than in those with low levels. This finding supports the importance of MDSC detection and targeting also in prostate cancer patients.
Topics: Male; Humans; Prostatic Neoplasms; Myeloid-Derived Suppressor Cells; Prognosis; Immunotherapy; Tumor Microenvironment
PubMed: 36411316
DOI: 10.1038/s41391-022-00615-5 -
Medicina (Kaunas, Lithuania) Aug 2022Background and Objectives: Advanced non-small-cell lung cancer (NSCLC) has led to a high number of mortalities. Immunotherapy, as a first-line treatment in advanced... (Meta-Analysis)
Meta-Analysis Review
Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Markers for Advanced Non-Small-Cell Lung Cancer Treated with Immunotherapy: A Systematic Review and Meta-Analysis.
Background and Objectives: Advanced non-small-cell lung cancer (NSCLC) has led to a high number of mortalities. Immunotherapy, as a first-line treatment in advanced NSCLC, currently has no clarity regarding its prognostic markers to assess the treatment outcome. This systematic review aimed to evaluate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in advanced NSCLC patients treated with immunotherapy. Materials and Methods: This systematic review was conducted using the PRISMA guidelines, starting from screening for relevant studies from several databases. Each included cohort study was further assessed by using the Newcastle−Ottawa Quality Assessment Scale, and the available data were extracted for qualitative and quantitative synthesis in pooled and subgroup analysis. Results: A total of 1719 patients were included in this meta-analysis. Hazard ratio (HR) outcomes for progression-free survival (PFS) and overall survival (OS) for NLR and PLR showed significant results, supporting NLR and PLR as prognostic markers (NLR: HR PFS 2.21 [95% CI: 1.50−3.24; p < 0.0001] and HR OS 2.68 [95% CI: 2.24−3.6; p < 0.0001]; PLR: HR PFS 1.57 [95% CI: 1.33−1.84; p < 0.00001] and HR OS 2.14 [95% CI: 1.72−2.67; p < 0.00001]). Subgroup analysis with a cut-off value of 5 for NLR and 200 for PLR also demonstrated notable outcomes. Higher NLR and PLR levels are associated with poor prognostic. Conclusions: There is considerable evidence regarding both markers as prognostic markers in NSCLC patients treated with immunotherapy. However, further studies with more homogeneous baseline characteristics are required to confirm these findings.
Topics: Carcinoma, Non-Small-Cell Lung; Cohort Studies; Humans; Immunotherapy; Lung Neoplasms; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies
PubMed: 36013536
DOI: 10.3390/medicina58081069 -
Maturitas Jan 2017A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated... (Review)
Review
OBJECTIVES
A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage.
METHODS
Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016.
RESULTS
Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity.
CONCLUSIONS
Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects.
Topics: Aged; Aging; Bone and Bones; Cognition; Cognition Disorders; Dietary Supplements; Humans; Osteoblasts; Osteoclasts; Osteoporosis; Prospective Studies; Tocotrienols
PubMed: 27889054
DOI: 10.1016/j.maturitas.2016.11.003 -
Frontiers in Oncology 2022Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully...
Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs' target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.
PubMed: 35330714
DOI: 10.3389/fonc.2022.848199